Method of detecting glaucoma

ABSTRACT

A method of testing for an ocular disease in an eye includes measuring a condition of the eye to receive a first value, placing an instrument adjacent the surface of the eye, changing the pressure in the eye using the instrument after measuring the condition, measuring the condition of the eye, after changing the pressure, to receive a second value, and comparing the first value to the second value.

This application is a continuation-in-part of application Ser. No.11/840,675, filed Aug. 17, 2007 now U.S. Pat. No. 7,549,752 entitled“Method of Glaucoma Detection”, the entire contents of which are hereinincorporated by reference.

BACKGROUND OF THE INVENTION

Progressive optic atrophy associated with excavation of optic nerve headis a hallmark of glaucoma that leads to visual field defects. Althoughincreased intraocular pressure is an obvious risk factor, the mechanismsthat lead to the damage of the optic nerve head is still a controversialissue, because glaucomatous optic nerve damage may develop at any levelof intraocular pressure. In the past Circulatory or vascular alterationshave been considered as a risk factor accounting for the development ofglaucomatous optic nerve damage. Fluorescein angiography (FAG) has shownfilling defects in the optic disc of eyes with NTG. Color Dopplerimaging (CDI) has demonstrated an increase in resistive index (RI) ofthe ophthalmic arteries in eyes with glaucoma. Laser Doppler analysisshowed a decrease in retinal and optic nerve flow in glaucoma patients.Further, measurements of pulsatile ocular blood flow (POBF) showed thePOBF to be significantly lower in NTG eyes with or without field lossthan in normal subjects.

SUMMARY OF THE INVENTION

The present invention relates to a method, including the steps ofmapping at least a portion of the fundus of the eye by forming aplurality of pixels, estimating the oxygen saturation level at each ofthe plurality of pixels, superimposing the fundus maps on maps ofanatomic borderlines, and comparing portions of the superimposed fundusmaps to predetermined fundus maps.

The present invention also relates to a method, including the steps ofmapping at least a portion of the fundus of the eye by forming aplurality of pixels using light from a spectral image system, dividingeach light beam from the light that is reflected from the fundus with aninterferometer into two coherent beams, recombining the two coherentbeams and detecting the interference, measuring the interference as afunction of the optical path difference, comparing the intensity of thelight to the optical path difference for each of the plurality ofpixels, estimating the oxygen saturation level at each of the pluralityof pixels, superimposing the fundus maps on maps of anatomic borderlinesand comparing portions of the superimposed fundus maps to predeterminedfundus maps.

Additional features and advantages are described herein, and will beapparent from, the following Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an image of a fundus showing seven areas where oxygensaturation (OS) level were measured;

FIG. 2 illustrates a map of the area of HFA used to calculate the meanof the total deviation (TD);

FIG. 3 illustrates oxygen saturation image maps;

FIG. 4 illustrates a comparison of the oxygen saturation levels at thesuperior, inferior, nasal, superotemporal, inferotemporaljuxta-papillary points, and the average of these five points among threegroups;

FIG. 5 illustrates oxygen saturation levels at 5 juxta-papillary pointsof a high tension subgroup;

FIG. 6 illustrates correlation between the mean of TD of the 17 pointsin the upper arcuate area and the oxygen saturation value at theinferotemporal point of the high tension subgroup;

FIG. 7 illustrates a correlation between MD and the averaged oxygensaturation value at the inferotemporal and the suprerotemporal points ofthe high tension subgroup; and

FIG. 8 is a side elevational view in section of a device that createspressure in the eye positioned adjacent the external surface of the eye.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a method in which the oxygen saturation(OS) levels in the fundus can be estimated non-invasively at each pixelwith about 35 degrees to about 100 degrees (or any other suitableamount) of fundus view. The method can be used on patients with centralretinal vein occlusion to evaluate the level of ischemia in the fundus.The oxygen saturation (OS) levels are measured quantitatively in theretina near the optic disc including the area corresponding to thearcuate retinal nerve fiber in eyes with open-angle glaucoma (OAG).

The oxygen saturation images can be obtained by spectral image (SRI)system. Generally, an SRI system instrument consists of a SD-200 opticalhead, which uses a Sagnac interferometer mounted on top of a funduscamera (TRC-50IA; Topcon Co., Tokyo, Japan) and a software moduleconsisting of an acquisition and an analysis module; however the SRIsystem can be any suitable system. Generally, the SRI system allows themeasurement of a spectrum in each pixel of the fundus image.

Preferably, after obtaining complete mydriasis with instillation of 0.5%tropicamide and 0.5% phenylephrine hydrochloride, the fundus is scannedby the camera for about 100 milliseconds to about 6 seconds using lightbetween 480 and 600 nm; however, it is noted that these parameters aremerely exemplary and can be any suitable parameters. Every light beamreflected from the fundus can be divided by the Sagnac interferometerinto two coherent beams, which can be recombined and the interferencedetected. The interference can then be measured by a detector as afunction of the optical path difference. The intensity versus opticalpath difference function, called an interferogram, can beFourier-transformed to achieve the spectral wave, which can be carriedout for every pixel of the image.

To estimate oxygen saturation level from the spectrum in each pixel, theapplicability of Beer-Lambert law can be assumed by constructing amathematical model to describe the measured fundus layers. For example,standard extinction coefficients of oxygenated and deoxygenatedhemoglobin (FIG. 1 a) and direct response in the system can besubstituted by a model based on Beer-Lambert, in which the oxygensaturation and blood column thickness are free parameters. Theseparameters can be then estimated to obtain the best fit between themodel and the actual measured spectrum (FIG. 1 b), yielding the oxygensaturation estimate for each pixel of the map. This transformation canbe carried out in every pixel to get an image map of the fundus in about35 degrees to about 100 degrees or any other suitable amount.

The oxygen saturation maps can then be superimposed on maps of anatomicborderlines by a separate analysis to serve as a guide and as a spatialcoordinating system. This can provide geographic maps, and the oxygensaturation pictures with which many physicians are familiar. Acquisitiontime with a spectral resolution of about 15 nm at about 500 nm can be atabout 100 milliseconds to about 6 seconds for a 284×244 pixel image;however, it is noted that these parameters are merely exemplary and canbe any suitable parameters. Using this technique and by applyingdifferent colors to different oxygen saturation level, red (e.g., about100%) to purple (e.g., about 40%), the fundus can represent twodimensionally. Coefficient variation of images taken with SRI system canbe examined and may be within 5%.

Using geographic maps, seven different points on the retina can beanalyzed, including retinal vessels to compare the values among lowtension and high tension subgroups and normal groups or any othersuitable groups. If desired, five juxta-papillary points (e.g.,superior, superotemporal, inferotemporal, inferior, and nasal point)with approximately 200.mu.m in diameter, avoiding the visible vessels inthe retina, and 200.mu.m in length along both retinal artery and thevein at 0.75 disc-diameter from the disc margin can be measured.However, it is noted that any number of juxta-papillary points can bemeasured having any desired and/or suitable dimensions.

The mean total deviation (TD) of oxygen saturation values can also becalculated at 17 points each in the upper and the lower arcuate area(FIGS. 2 a and b), 5 points upper and lower to the blind spot (FIGS. 2 cand d), and 4 points temporal to the blind spot related to the opticdisc (FIG. 2 e). These five regional TD values can correlate the oxygensaturation value at five measurement points respectively. Please notethat any number of points each in the upper and the lower arcuate areacan be used and in any areas desired.

Oxygen saturation measurement using a Fourier-transform-based SRI systemcan show the oxygen saturation level to be significantly lower in OAGeyes compared with normal eyes. In low tension subgroups, decreasedoxygen saturation levels in the juxta-papillary area can be evident andcan be observed in 3 measurement points (superior, nasal andinferotemporal point) out of five points, while the oxygen saturationlevel at only inferotemporal point can be significantly low in hightension subgroups.

Generally, there is no difference between the low tension and the hightensions subgroups by means of several HFA calculations, thus theseverity of these two groups' glaucoma can be estimated to be about thesame. Nevertheless, there can be a difference in oxygen saturationlevels between the two subgroups, although the oxygen saturation levelin the retinal artery, vein, and the difference between them in all thegroups may be the same. The decreased oxygen saturation level inrelationship with the retinal function may be related to development ofglaucoma especially in normal tension glaucoma (NTG).

Patients with NTG have vasospastic episodes, often disc hemorrhages andperipapillary chorioretinal atrophy. In addition, higher endothelin-1plasma levels in NTG patients than high-tension glaucoma patients havebeen reported. Decreased OS level in the juxta-papillary area may bepresent in NTG patients even before the visual field-loss becomesevident.

In the high tension group, oxygen saturation level can be significantlydecreased at the inferotemporal point compared to normal subjects. Among5 juxta-papillary measurement points, the oxygen saturation levels atinferotemporal, superotemporal, and inferior points were lower thanthose at nasal point. Averaged oxygen saturation value at inferotemporaland superotemporal points can be significantly correlated with the meandeviation. Additionally, the TD in the upper arcuate area (relating toinferotemporal point), may show good correlation with low oxygensaturation level at corresponding juxta-papillary area with astatistical significance. The decreased oxygen saturation levels atperi-papillary area may have resulted in decreased retinal sensitivityin HVF, in the high tension and in NTG patients.

Different oxygen saturation levels in the peripapillary area may beobserved among low tension, high tension and normal eyes and alsoaltered relation between the oxygen saturation level and HVF analysis inlow tension and high tension glaucoma patients. Oxygen saturationmeasurement can be also a useful method in evaluation and potentiallymanagement of OAG patients.

FIG. 8 illustrates another embodiment in which glaucoma can be detectedusing a device 20 and method that increases pressure in the eye 10. Thedevice 20 can increase pressure by creating suction and/or a vacuum at aportion on the eye. For example, the device can be positioned at or nearthe cornea and/or the sclera or at any other suitable position on theeye. Additionally, if desired, the device can apply pressure to the eye,thus increasing the pressure.

The device to increase the pressure can be substantially circular withan arcuate inner surface 22 and an outer surface 24. That is, thesurface that is positioned adjacent the cornea and/or sclera can have anarcuate surface or any other suitable surface. The radius of curvatureof the arcuate surface can be about the same as the curvature of the eyeor have a steeper or shallower radius of curvature of the eye. Thedevice can be formed of any suitable material and be formed fromtransparent, translucent or opaque material.

To apply the vacuum, a pump 26 can be attached or coupled to the deviceuse a tube 28 or any other suitable means. The pump through tubing cancreate suction within the space 30 between the device and the eye,thereby creating a vacuum. This vacuum will increase the pressure in theeye.

A similarly shaped device can be used to increase the pressure in theeye by applying pressure to the external surface 24 of the device.

It is noted that any suitable device to increase pressure can be used inthis procedure.

Preferably, the pressure in the eye is gradually raised to between about1 mm Hg to about 30 mm Hg, and more preferably to between about 3 mm Hgto about 10 mm Hg or to any specific pressure within or without of theseranges or any suitable range therein. For example, the pressure can beraised to 6 mm Hg, if desired or any pressure outside of the abovestated range, if suitable. The pressure is maintained at the desiredamount for a predetermined time. For example, the pressure can bemaintained for about 5 to about 10 seconds or up to about 1 minute, orany other specific suitable time or range of times. Before, during andafter the increase in pressure, the oxygen saturation levels aremeasured and compared and/or contrasted to a normal eye or any otherdetermined amount.

If desired, the pressure can be reduced and the oxygen saturation levelscan be monitored to determine the length of time that is required forthe levels to return to normal or substantially normal level. This typeof stress test will indicate whether a patient has glaucoma.

The difference between oxymetry values (i.e., oxygen saturation levels)in sitting vs. laying down position can also be indicative of glaucoma.

EXAMPLES

The oxygen saturation level of each point was masked as to the subjects'characteristics. Unpaired t-test or non-repeated measures of ANOVAfollowed by Bonferroni correction or repeated measures of ANOVA followedby Student-Newman-Keuls test was used for statistical evaluation.

Fifty-six eyes of 56 Japanese OAG patients and 20 eyes of 20 normalJapanese were recruited for the study. Among 56 OAG eyes, 15 eyes (15patients) constantly showed recorded intraocular pressure (IOP) of.Itoreq. 15 mmHg and were classified as low-tension (LT) subgroup. Theother 41 eyes from 41 patients showed recorded IOP of .gtoreq.22 mmHg inmultiple readings and were classified as high-tension (HT) subgroup,during more than 6 of months follow-up. The subjects age were 27 to 73(mean .+−.SD, 60.5.+−0.11.9) years in the LT subgroup, 22 to 78(55.9.+−0.14.8) years in the HT subgroup, and 31 to 79 (52.6.+−0.15.7)years in the normal group. The differences in the mean ages among thethree groups were not statistically significant (p>0.05, non-repeatedmeasures of ANOVA).

All patients underwent routine ophthalmic examination previous to thisstudy. There was no obvious change in normal group except for mildsenile cataract and refractive error. Patients who had a history ofsystemic diseases such as systemic hypertension or diabetes mellituswere excluded from this study. Additionally, all LT patients wereexamined by CT scan or by magnetic resonance images (MRI) that showednormal results. This study was carried out with approval from the reviewboard of the institute and informed written consent was obtained fromall the patients. All but two patients had never taken any instillationof medication to lower the IOP, and those who had been taking it werewithheld from it for at least 4 weeks before entry in this study. AllOAG patients had visual field examination with automatic staticperimetry at least twice that showed characteristic glaucoma visualfield losses in all. A Humphrey field analysis (HFA) with the program30-2 SITA (Zeiss Humphrey Instruments, Dublin, Calif., USA) wasperformed. The oxygen saturation (OS) level in the fundus was measuredwith Fourier-transform-based spectral retinal image (SRI) system(Retinal Cube; ASI Co. Migdal Hemak, Israel) around noon till 3 o'clockin the afternoon.

Results

The intraocular Pressure (IOP) of all subjects was measured using aGoldmann applanation tonomer (Haag-Streit, Berne, Switzerland) justbefore the OS level measurement. It averaged 12.9.+−0.1.4 mmHg in the LTsubgroup, 20.0.+−0.4.1 mmHg in the HT subgroup, and 14.0.+−0.2.8 mmHg inthe normal group. The differences among the HT subgroup and the othertwo were statistically significant (p<0.001).

The average of the mean deviation (MD) of the light intensity was−8.4.+−0.6.5 dB in the LT subgroup and −7.7.+−0.6.9 dB in the HTsubgroup. The mean of total deviation (TD) of 17 points in the upperarcuate and in the lower arcuate area respectively, that of 5 pointsupper to the blind spot, that of 5 points lower to the blind spot, andthat of 4 points temporal to the blind spot was −9.9.+−0.9.−7.5.+−0.6.,−6.5.+−0.7., −6.4.+−0.8., and −4.7.+−0.7. dB in the LT subgroup and−7.9.+−0.9.0, −8.6.+−0.8.−4.0.+−0.6., −4.7.+−0.5., and −3.4.+−0.6. dB inthe HT subgroup, respectively. All of these HFA results showed nosignificant difference between the two OAG subgroups (unpaired t-test).

In the normal eyes, OS map demonstrated dominantly yellow to red, with afew green color dots surrounding the optic disc (FIG. 3 a) thatsuggested OS levels of the retina at corresponding area were higher than80%. In contrast, green and/or blue dots overriding in OS maps of the LTsubgroup implied OS levels in the retina to be approximatedapproximately from 70% to 80% (FIG. 3 c). Whereas OS levels in the HTsubgroup were more variable than in the LT subgroup, averaged colorrange lay in the middle of the normal group and the LT subgroup in mostof eyes (FIG. 3 b). The edge of vessels and rim of the disc wereartificially delineated to make them clearer. OS levels in the retina at5 points in the juxta-papillary retina, as well as in both the retinalartery and vein, were summarized in Table 1 and FIG. 4.

OS levels of both the LT and the HT subgroups were significantly lowerthan those of the normal group at the inferotemporal point and than theaveraged OS value of the juxta-papillary five points(p=0.047.about.0.001). At the superior and nasal points, OS level of theLT subgroup showed significant decreases as compared with the HTsubgroup (p=0.026 and 0.048 respectively) and also those of the normalgroup (p=0.009 and 0.019 respectively). Except the inferior and thesuperotemporal points, the OS levels at juxta-papillary area of both HTand LT subgroups were lower than those of normal subjects.

OS levels in the retinal artery and vein showed no significantdifferences among these three groups. The value of OS level reductionbetween artery and vein (artery-vein) also showed no significantinter-group difference (Table 1).

Differences of OS levels among the 5 juxta-papillary points were thenexamined. There were no statistically significant differences in thenormal group and the LT subgroup. On the other hand, in the HT subgroup,inferior, superotemporal, and inferotemporal points were significantlylower as compared with nasal point (<0.010, p<0.050, p<0.010,respectively; FIG. 5).

There was a statistically significant correlation between the mean of TDof the 17 points in the upper arcuate area and the OS level of theinferotemporal point (p=0.018, r=0.377; FIG. 6, table 2) in the HTsubgroup. The correlation between MD and the averaged OS value of theinferotemporal and the superotemporal point was also statisticallysignificant (p=0.037, r=0.334; FIG. 7). No significant correlation wasobserved between MD and the averaged OS value of the 5 juxta-papillarypoints, or between the mean of TD of 17 points in the lower arcuate areaand the OS level at the superotemporal point. In the LT subgroup, nosuch correlation was present (Table 2).

TABLE 1 Normal LT HT Superior 88.5 ± 11.1 76.6 ± 10.2 84.4 ± 11.4Inferior 84.8 ± 9.6 81.5 ± 9.7 82.3 ± 11.0 Nasal 91.8 ± 8.9 77.2 ± 11.085.1 ± 14.1 Superotemp. 88.4 ± 11.1 81.7 ± 9.4 81.5 ± 12.1 Inferotemp.86.3 ± 10.2 73.0 ± 10.9 80.2 ± 12.1 Average 87.6 ± 8.2 77.8 ± 7.6 82.4 ±9.8 Artery 85.5 ± 14.1 85.5 ± 7.9 85.3 ± 7.7 Vein 68.5 ± 8.0 62.8 ± 8.065.2 ± 8.0 Artery-Vein 17.2 ± 11.5 22.8 ± 12.5 20.7 ± 8.0

TABLE 2 p r Mean of TD of Area a and HT 0.0179 0.377 Inferotemporal OSLT 0.6478 0.134 Mean of TD of Area b and HT 0.6786 0.067 SuperotemporalOS LT 0.9468 0.019 MD and HT 0.1569 0.225 Average OS LT 0.6277 0.136 MDand Average of HT 0.0374 0.334 Infertotemporal and LT 0.9783 0.030Superotemporal OS

It has been shown that prophylactic treatment of many diseases canmaintain health for a long time, and at times manifestation of thedisease can be prevented completely. In addition certain diseases suchas glaucoma, degenerative retinal, optic nerve disorders and celldegenerations are difficult to predict until the diseases havemanifested and have caused irreversible damage. These eye diseases arein need of early diagnosis. The purpose of this invention is to providemeans of uncovering the precesses that would have remained undetected bythe standard test. In other words, the present embodiment relates to astress test applied to these predisposed conditions so that the diseasecan be detected early and treated prophylactically.

In some embodiments described herein, a test along with oxymetry of theretina-choroid is used. In the current embodiment, an instrument isapplied along with other standard examination units such as visualacuity, electroreinography and perimetry etc. In this embodiment, acondition of the eye is measured at various intervals. For example, thecondition may be measured before the instrument is applied and/orpressure is applied to the eye to determine a first value, afterpressure has been applied to determine a second value, and/or after apredetermined time to determine a third value and/or the rate of returnto the first value. Each of the first, second and third values can becompared to one another.

Electroretinography may evaluate the electrical responses of retinalcells to a light stimulus. Electrodes are usually placed on the corneaand on the forehead. A standard light stimulus is used to initiateelectrical activity of the retinal cells which is displayed showing thetime course of the signal's amplitude (voltage) in microvolts or lower.Various stimuli can produce a more specific response from certainretinal cells such as flash or pattern, background light, the colors ofthe stimulus and background.

In a dark-adapted condition, a rod response may be primarily obtainedand in a light adapted state the ERG may show the cone response. The ERGwaves are a-wave (photoreceptor) and b-wave (bipolar, Muller cells etc).The pattern ERG reflects the activity of the ganglion cells.

Multifocal ERG records ERG or VER from stimulation of different retinallocations. Each visual field location is stimulated with a separatestimulus in a different sequence. Therefore the ERG and VER can beanalyzed using mathematical algorithm. e.g. Multifocal Electroretinogram(mfERG) MfERGs were recorded with the VERIS™ Science 5.1.12 (EDI:Electro-Diagnostic Imaging, San Mateo, Calif.). The recordings areperformed under ordinary room light with the pupil dilated maximally.The stimulus is displayed on a monochrome CRT with a P4 (white)phosphor. An array of 37 densely packed hexagons stimulates the central40° of the visual field (stretch factor was 13.18). An m-sequence rateof 75/s and cycle of 2¹⁴ −1 steps results in a recording time of 3′38″(net). The stimulus intensity is 2.67 cd·s/m². Responses are recordedwith a Burian-Allen bipolar contact lens electrode. A Camera/Refractor™(Electro-Diagnostic Imaging) is used for refraction and to monitor eyeposition and fixation stability during the recordings. The signals areamplified (100,000×), band-pas filtered (10-300 Hz at half-amplitude)and digitalized with a 1,200 Hz sampling frequency. Density-scaled[nV/deg²] amplitudes between first negative and first positive peaks ofthe first-order kernel (K1) are analyzed.

Perimetry measures differential light sensitivity in the visual fieldand its boundaries of the retina while the subject's gaze is fixed. Onecan use either a manual technique or more sophisticated units to doperimetry or a kinetic perimetry. For detection of visual fields loss ormore subtle changes in the visual field, one can perform a thresholdperimetry that can be evaluated within days, weeks, months, etc. with anautomated unit. This technology has been used for detection and followup of the diseases of the brain, optic nerve and retinal diseases suchas glaucoma or age related macular degeneration/degenerative retinaldiseases.

Visual acuity testing is now a standard of every optometry ofopthalmology office and the techniques are known. The visual acuity isaffected in all diseases and affects the central retina macula, and/orthe optic nerve. This includes degenerative, inflammatory vascular andinherited diseases and toxicity of medications. In one embodiment, thevisual acuity is determined at one or a plurality of times. For example,the visual acuity can be determined before and/or after the test.

Until now this instruments has not been used as a predictive in officetests for evaluation of ocular diseases such as glaucoma or optic nerve.

The test is some embodiments discussed herein utilizes an instrumentsuch as a suction cup to increase the intraocular pressure (5-25 mg Hgor more) for a short period of time (1-10 minutes or more). The ERG,Perimetry or Oxymetry can be performed before and after the rise in theintraocular pressure. In normal subjects the full recovery of visualfunction including, visual acuity, ERG or multifocal ERG andperimetry/visual evoked response or visual evoked potential occurs muchfaster than a diseased or an eye predisposed to the diseased condition.A group of age matched healthy volunteers have been tested by the abovementioned techniques to create a standard value for each test. Asignificant alteration between the normal values in the suspected orpredisposed to disease eye and normal aged matched subjects isconsidered as pathological or predisposed to the pathology. In ERG thiscan manifest itself in delay in recovery of a and b waves of the ERG orother changes, in perimetry it presents as a delay in recovery of thevisual field in boundaries or threshold of the examined retinalsensitivity, or delayed in recovery of the visual acuity compared to thenormal subjects.

The instrument for elevating the intraocular pressure can be a suctioncup, contact lens or a hollow tube to which suction is applied andtransmitted to the eye. It can also be a unit that pushes or applies apredetermined pressure on the eye for a given period. For example, theinstrument can be any instrument herein described for altering orchanging the pressure in the eye. This instrument can be equipped with apressure sensor, indication the intraocular pressure or one can measurethe pressure with another independent unit before or during theevaluation. The methodology can be used by a person skilled in the artwith any other means or modifications.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

1. A method of testing for an ocular disease in an eye, comprising;measuring a stimulus of the eye to receive a first value; placing aninstrument adjacent the surface of the eye; changing the pressure in theeye using the instrument after said measuring the condition to receive afirst value; measuring the stimulus of the eye, after said changing thepressure, to receive a second value; and comparing the first value tothe second value.
 2. A method according to claim 1, wherein each of saidmeasurings includes placing electrodes on the cornea and forehead of apatient, initiating electrical activity of the retinal cells,determining one of a cone response and a rod response.
 3. A methodaccording to claim 2, wherein said initiating electrical activityincludes using a light stimulus.
 4. A method according to claim 2,wherein the activity of the retinal cells is displayed illustrating thetime course of an amplitude of a signal in microvolts.
 5. A methodaccording to claim 1, wherein each of said measurings includes measuringa stimulus response of a plurality of visual field locations, eachvisual field location being stimulated with a separate stimulus.
 6. Amethod according to claim 5, further comprising monitoring eye positionand fixation stability during each of said measurings.
 7. A methodaccording to claim 5, wherein said comparing includes comparing densityscaled amplitudes between first negative and first positive peaks offirst order kernels.
 8. A method according to claim 5, wherein each ofsaid measurings includes measuring the stimulus response of a pluralityof densely packed hexagons disposed in the central 40° of the visualfield.
 9. A method according to claim 1, wherein each of said measuringsincludes measuring differential light sensitivity in the visual field ofthe retina of the eye and boundaries of the of the visual field of theretina while the position of the eye is fixed.
 10. A method according toclaim 1, wherein said instrument is one of a suction cup, a contact lensand a hollow tube.
 11. A method according to claim 1, further comprisingmeasuring the condition of the eye to receive a third value after saidmeasuring the condition of the eye to receive a second value; andcomparing the first, second and third values.
 12. A method according toclaim 11, further comprising waiting a predetermined time before saidmeasuring the condition of the eye to receive a third value.
 13. Amethod according to claim 1, further comprising determining the visualacuity before said placing an instrument and after said changing thepressure.